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HAND 中的脑白质损伤、神经炎症和神经元完整性。

White matter damage, neuroinflammation, and neuronal integrity in HAND.

机构信息

University of California at San Diego, La Jolla, CA, USA.

University of Washington, Seattle, WA, USA.

出版信息

J Neurovirol. 2019 Feb;25(1):32-41. doi: 10.1007/s13365-018-0682-9. Epub 2018 Oct 5.


DOI:10.1007/s13365-018-0682-9
PMID:30291567
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6416232/
Abstract

HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds ratios were used to compare HAND to NU. Among 253 participants, 40% met HAND criteria (21% ANI, 15% MND, and 4% HAD). Higher risk of HAND was associated with more aWM. Both HAD and MND also had smaller gray and white matter volumes than NU. Among individuals with undetectable plasma HIV RNA, structural volumetric findings were similar to the overall sample. MND had lower FWM creatine and higher FGM choline relative to NU, whereas HAD and ANI had lower BG N-acetyl aspartate relative to NU. In the virologically suppressed subgroup, however, ANI and MND had higher FGM choline compared to NU. Overall, HAND showed specific alterations (more aWM and inflammation; less gray matter volume and lower NAA). Some MR measures differentiated less severe subtypes of HAND from HAD. These MR alterations may represent legacy effects or accumulating changes, possibly related to medical comorbidities, antiretroviral therapy, or chronic effects of HIV brain infection.

摘要

HIV 相关的神经认知障碍(HAND)即使在联合抗逆转录病毒治疗(cART)下病毒学抑制后仍然存在,其潜在的病理生理机制尚不清楚。我们对没有主要神经认知合并症的 HIV 阳性个体进行了结构磁共振成像和磁共振波谱(MRS)检查。研究参与者被分为神经认知正常(NU)、无症状(ANI)、轻度认知障碍(MND)或 HIV 相关痴呆(HAD)。使用结构 MRI,我们测量了皮质和皮质下灰质以及总白质和异常白质(aWM)的体积。使用单体素 MRS,我们估计了额状灰质(FGM)和额状白质(FWM)以及基底节(BG)区域的代谢物。使用调整后的优势比比较 HAND 与 NU。在 253 名参与者中,40%符合 HAND 标准(21% ANI、15% MND 和 4% HAD)。HAND 的风险较高与更多的 aWM 相关。HAD 和 MND 的灰质和白质体积也比 NU 小。在血浆 HIV RNA 不可检测的个体中,结构体积发现与总体样本相似。与 NU 相比,MND 的 FWM 肌酸较低,FGM 胆碱较高,而 HAD 和 ANI 的 BG N-乙酰天冬氨酸较低。然而,在病毒学抑制亚组中,ANI 和 MND 的 FGM 胆碱比 NU 高。总体而言,HAND 表现出特定的改变(更多的 aWM 和炎症;更少的灰质体积和更低的 NAA)。一些磁共振测量区分了 HAND 不太严重的亚型与 HAD。这些磁共振改变可能代表遗留效应或累积变化,可能与医疗合并症、抗逆转录病毒治疗或 HIV 脑感染的慢性影响有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/6416232/f2363acb4578/13365_2018_682_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/6416232/bc8ef7fc6ecd/13365_2018_682_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/6416232/1eaf86fd89fb/13365_2018_682_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/6416232/77f1078adc24/13365_2018_682_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/6416232/acd9f2c37a0b/13365_2018_682_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/6416232/f2363acb4578/13365_2018_682_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/6416232/bc8ef7fc6ecd/13365_2018_682_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/6416232/1eaf86fd89fb/13365_2018_682_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/6416232/77f1078adc24/13365_2018_682_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/6416232/acd9f2c37a0b/13365_2018_682_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140d/6416232/f2363acb4578/13365_2018_682_Fig5_HTML.jpg

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